Ten Commandments for Randomized Trials of Pharmacological Therapy for COPD and Other Lung Diseases.

The randomized controlled trial is the quintessential scientific tool to evaluate the effectiveness and safety of medications. While early trials of drugs used for the treatment of chronic obstructive pulmonary disease (COPD) and other respiratory diseases were generally unambiguous, more recent studies have been controversial. It has become evident that the conduct, design and analysis of these trials were highly variable and may have been responsible for incoherencies in results and interpretation. With the advent of new studies, the need for guiding principles for the conduct of future randomized trials has become manifest. We describe the concept of the counterfactual principle as it applies to the treatment of patients and to the randomized trial. We then present ten methodological tenets for the design and statistical aspects of randomized controlled trials evaluating the effectiveness of drugs used in the treatment of several respiratory diseases. They include eight study design and two statistical analysis principles: 1) Study question; 2) Intervention; 3) Study population; 4) Blinding; 5) Run-in period; 6) Follow-up; 7) Outcome; 8) Safety; 9) Intent-to-treat; 10) Covariate adjustment. These tenets are described using mainly examples from trials of pharmacological treatments for COPD, as well as some from asthma and idiopathic pulmonary fibrosis, conducted over the last 30 years. The careful application of these principles in the conduct of randomized trials will provide rigorous studies and improve the validity of results. The ensuing clearer interpretation of findings will permit their well-founded contribution to treatment guidelines and optimal clinical management.